Treatment Guidelines for Haemophilia in South Africa

These guidelines have been compiled by the South African Haemophilia Foundation Medical and Scientific Advisory Council (SAHF MASAC) to facilitate the appropriate management of people with haemophilia (PWH). The current guidelines are based on the publication noted below.

Note to Healthcare Personnel

This booklet is intended as a guide for healthcare personnel who might not be familiar with haemophilia. People with haemophilia (PWH) and their physicians should be advised by a Comprehensive Haemophilia Treatment Centre staffed by a multidisciplinary team skilled in the care of this uncommon chronic bleeding disorder.

Parents of patients with severe haemophilia are usually trained in home infusion of the clotting Factor when their child is about four years old and self infusion is normally accomplished by 12 – 14 years of age. However, infants and boys with mild haemophilia must rely on a Haemophilia Centre or other medical facility for clotting Factor infusions.

Haemophilia Overview

Haemophilia is an inherited, x-linked, lifelong bleeding disorder which affects males almost exclusively. Most frequently haemorrhage involves joints or muscles. Bleeding patterns differ with age: infants usually bleed into soft tissues or from the mouth but as the boy grows, characteristic joint bleeding becomes more common.

Haemophilia A is the most common form of haemophilia and is due to a deficiency of clotting Factor VIII.

Haemophilia B is due to a deficiency of clotting Factor IX.

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Severity

Haemophilia is classified as severe, moderate, or mild according to the levels of circulating Factor VIII or IX and indicates the expected frequency of bleeding:

Severe:

Factor VIII or IX < 1%

Factor VIII or IX replacement is needed several times per month for traumatic or apparently spontaneous bleeding may be on regular prophylactic factor therapy.

Moderate:

Factor VIII or IX 1 – 5%

Less frequent bleeding which usually follows trauma, surgery or dental work.

Mild:

Factor VIII or IX > 5 – < 40%

Occasional bleeding, usually only after severe trauma or surgery.

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Factor VIII Inhibitors in Haemophilia

Inhibitors may develop in 10 – 15% of persons with haemophilia A but are much less common in haemophilia B (1 – 3%). Inhibitors are neutralising antibodies that limit the effectiveness of Factor infusions.

Risk Factors for the development of inhibitors:

severe haemophilia

family history of inhibitor development

more frequent in black patients

If an individual is going to develop an inhibitor, this usually happens within the first 50 exposure days after starting Factor VIII replacement therapy.

Rules for Inhibitor Management

Monitor all patients every 3 – 6 months for the development of inhibitors. This is particularly important and should be done more frequently in newly diagnosed black patients with severe haemophilia A, who are at greater risk.

Never undertake a surgical procedure or joint aspiration in a person with haemophilia without checking for inhibitors.

If there is no response to appropriate replacement therapy, test for inhibitors.

Post Partum

Notes:

Genetics

Genetic testing for haemophilia A and B is important for:

Definitive carrier testing

Prenatal counselling and testing

Definitive carrier testing:

All females who are at risk of being haemophilia carriers (mother, sisters, maternal aunts and maternal aunts’ daughters of a person with haemophilia) should be offered genetic counselling and testing, so that their carrier status can be determined definitively. This can be done in early childhood, so that pre-emptive management is possible, but with appropriate consent and genetic counselling.

Females who are shown to be carriers or high-risk can then be managed appropriately for bleeding complications

Females who are non-carriers or at low risk would be at very low risk of bleeding complications

Prenatal counselling and testing:

Females who are shown to be carriers or high-risk should be offered genetic counselling when they reach child-bearing age to discuss their risks and options for prenatal testing and pregnancy management

Genetic testing

Is complex

May be done by direct mutation analysis or gene tracking (linked marker) analysis

May require blood samples from a number of family members (including unaffected individuals)

Consult with a Genetics Centre to determine from which family members samples are required

High Responder (> 5 BU)
Both APCC and rVIIa are effective for treatment of acute bleeding episodes in patients with Factor VIII inhibitors.

Activated Prothromibin Complex Concentrate (APCC)
Dose: 50 – 100 IU/kg q12 – 24h for 3 days or until clinical improvement Infuse at 2 IU/kg/min
Do not exceed a single dose of 200 IU/kg

Do not use antifibrinolytic drugs (e.g. tranexamic acid) concurrently because of the risk of thromboembolism

Recombinant Factor VIIa (rFVIIa)
90 μg per kg q2 – 3 h or by continuous infusion (at 20 μg/kg/hr) until clinical improvement.
Factor VIIa activates Factor X and leads to the formation of a haemostatic plug.
New single dose of 270 μg/kg may be used

2. Long term Management – Immune tolerance (IT)

Several regimens are effective – the Dutch regime
(25 IU Factor VIII/kg 3 times per week) is the most affordable.

Haemophilia B

Treatment of haemophilia B with inhibitors

An aPCC should be carefully monitored for anaphylaxis and anamnestic reaction. Therefore patients with haemophilia B and inhibitors are best treated with rFVIIa, the only bypassing agent that does not contain FIX.

There is no evidence to guide tolerisation procedures in patients with haemophilia B and inhibitors. Plasma-derived FIX may be used for tolerisation with careful monitoring of anaphylactic reactions

Treatment with rFVIIa:

Give dose of 90 – 120 μg/kg IV every 2 – 3 hours as bolus or 20 IU/kg/hour as continuous infusion. Single dose of 270 μg/kg may be used.